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Innovative Biocomputational Approach to Decode the Secrets of the 2022 Monkeypox Resurgence

JSHS · 2023

Overview

In mid-2022, a new outbreak of Mpox circulated the world—this time with high infectiousness and transmissibility. In just six months, 30,000 cases were reported. As we recovered from COVID-19, fear of another pandemic heightened. Two fundamental questions emerged: What caused Mpox to increase its infectivity, and what structural changes might have contributed?; Will changes in the protein structure affect efficacy of drugs? Experimental studies can take years to answer these questions. By using biocomputational science, we get answers within weeks. A significant bottleneck was lack of basic three-dimensional protein structures for the Mpox replication complex, which makes copies of DNA. My investigation consisted of three objectives: (i) predicting structure of Mpox replication complex, (ii) identifying mutations in the virus that appeared in the outbreak, and (iii) identifying causative factors for increased transmissibility and effectiveness. I used a "lego-brick" approach to protein structure elucidation and developed advanced biocomputational tools for identifying mutational patterns. Among the five components of the minimal replication complex, ten mutations were observed. Two mutations, L108F and W411L, in DNA polymerase play a critical role. Notably, L108F in DNA polymerase protein (apparent only in current outbreak) increases binding affinity between protein and DNA. Both mutations could be crucial to the virus's infectivity. Further, I identified mutational regions in the Mpox virus that could confer resistance. Despite focusing on Mpox, the method and biocomputational model presented can be applied across many areas. Causative factors can be predicted using these methods for any such virus and, thus, future pandemics.

Competition history

  • JSHS 2023 Category not listed

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